AAPS PharmSciTech

, Volume 19, Issue 8, pp 3571–3583 | Cite as

Novel Self-Assembled Ibrutinib-Phospholipid Complex for Potently Peroral Delivery of Poorly Soluble Drugs with pH-Dependent Solubility

  • Qiujun Qiu
  • Mei Lu
  • Cong Li
  • Xiang Luo
  • Xinrong Liu
  • Ling Hu
  • Mingqi Liu
  • Huangliang Zheng
  • Hongxia Zhang
  • Min Liu
  • Chaoyang Lai
  • Yanzhi SongEmail author
  • Yihui DengEmail author
Research Article Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
Part of the following topical collections:
  1. Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery


As an irreversible small-molecule kinase inhibitor, ibrutinib (IBR) exhibits excellent tumor suppression in various tumor cells. However, IBR is insoluble at neutral pH and can dissolve only at low pH: thus, commercial IBR products present poor bioavailability and weakened in vivo antitumor activity. Therefore, we aimed to develop a stable IBR-phospholipid complex (IBR-PC) using egg phosphatidylglycerol (EPG) as excipients to improve the bioavailability of IBR and further enhance its antitumor effects. IBR-PC was characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XPRD), and molecular docking and simulation test, which all explained the interactions of two components. Solubility tests demonstrate that the novel formulation can maintain excellent solubility (above 5 mg/mL) at various pH levels. Storage stability tests show that no change in particle size or content of IBR-PC was observed during the experimental period. In vivo pharmacokinetic results demonstrated that the relative bioavailability of IBR-PC was a 9.14-fold improvement relative to that of IBR suspension (IBR-susp). Furthermore, IBR-PC was associated with enhanced cytotoxic activity in vitro and superior tumor growth suppression in vivo compared to that resulting from the free IBR. Thus, the proposed IBR-PC system is a promising drug delivery system that enhances the oral bioavailability of IBR, resulting in its improved in vivo antitumor effect.


ibrutinib phospholipid complex egg phosphatidylglycerol bioavailability antitumor activity 



This research was supported by the National Natural Science Foundation of China (No. 81373334 and No. 81573375).

Compliance with Ethical Standards

All animal experiments were performed in accordance with the guidelines of the Animal Welfare Committee of Shenyang Pharmaceutical University. The protocol numbers of the animal studies were SYPU-IACUC-C2018-1-24-201 and SYPU-IACUC- C2018-4-4-101.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Qiujun Qiu
    • 1
  • Mei Lu
    • 1
  • Cong Li
    • 1
  • Xiang Luo
    • 1
  • Xinrong Liu
    • 1
  • Ling Hu
    • 1
  • Mingqi Liu
    • 1
  • Huangliang Zheng
    • 1
  • Hongxia Zhang
    • 1
  • Min Liu
    • 1
  • Chaoyang Lai
    • 1
  • Yanzhi Song
    • 1
    Email author
  • Yihui Deng
    • 1
    Email author
  1. 1.College of PharmacyShenyang Pharmaceutical UniversityShenyangChina

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